Even Mild COVID-19 Can Leave Lasting Brain Damage, Study Finds

A new study suggests that recovery from COVID-19 may not end when respiratory symptoms fade.

A mild bout of COVID-19 or influenza may have effects that continue long after obvious symptoms such as fever and coughing disappear. New research from Tulane University suggests these hidden changes could help explain why some people do not feel fully recovered for weeks or even months.

The research team found that both viruses can cause lasting damage in the lungs. However, only infection with SARS-CoV-2 was linked to ongoing inflammation in the brain and injury to tiny blood vessels, even after the virus could no longer be detected. The study, published in Frontiers in Immunology, offers insight into why long COVID is often marked by brain-related symptoms such as brain fog, fatigue, and mood changes, while influenza is more frequently associated with breathing problems.

“Influenza and COVID-19 affect large populations worldwide and carry a significant public health toll, yet the mechanisms behind their long-term effects remain poorly understood,” said Dr. Xuebin Qin, lead author and professor of microbiology and immunology at the Tulane National Biomedical Research Center.

Comparing the Lingering Effects of Two Viruses

To determine which aftereffects are shared by serious respiratory infections and which are specific to COVID-19, the scientists used a mouse model. They analyzed lung and brain tissue after the infections had fully cleared.

In lung tissue, the two viruses produced similar long-term patterns. Immune cells remained active instead of returning to a resting state, and collagen levels increased. Collagen is a structural protein linked to scar formation. Its buildup can stiffen lung tissue and make breathing more difficult. This may help explain why some people experience prolonged shortness of breath after respiratory illnesses.

A closer look revealed an important difference. After influenza infection, the lungs appeared to begin a structured repair process. Specialized cells moved into damaged regions to rebuild the airway lining. This recovery response was largely absent following SARS-CoV-2 infection, suggesting that COVID-19 may disrupt the lungs’ ability to heal properly.

Persistent Brain Changes After COVID-19

The most striking differences appeared in the brain.

Neither virus was detected in brain tissue. However, mice that had recovered from COVID-19 showed signs of ongoing brain inflammation weeks later. Researchers also observed small areas of bleeding. An analysis of gene activity showed continued inflammatory signaling and disturbances in pathways that regulate serotonin and dopamine, which play key roles in mood, thinking, and energy. These changes were mostly absent in animals that had influenza.

“In both infections, we observed lasting lung injury,” Qin said. “But long-term effects in the brain were unique to SARS-CoV-2. That distinction is critical to understanding long COVID.”

The study was supported by an American Heart Association award Qin received as part of a national effort to understand the long-term cardiovascular and cerebrovascular effects of COVID-19. The results provide new evidence that changes in blood vessels and immune responses may contribute to ongoing neurological symptoms.

By identifying these biological patterns, the researchers hope to improve how patients are monitored after infection and guide the development of treatments that could limit lasting harm. As persistent symptoms continue to affect many people, clarifying the underlying causes remains essential to reducing the long-term health impact.

Reference: “Characterization of subchronic lung and brain consequences caused by mouse-adapted SARS-CoV-2 and influenza A infection of C57BL6 mice” by Joshua Currey, Chenxiao Wang, Meredith G. Mayer, Yilin Chen, Ana Karina Nisperuza Vidal, Michaela J. Allen, Mst Shamima Khatun, Calder R. Ellsworth, Mohammad Islamuddin, Jefferson Evangelista, Skye M. Minor, Nadia Golden, Kevin J. Zwezdaryk, Nicholas J. Maness, Robert V. Blair, Jay K. Kolls, Derek A. Pociask, Tracy Fischer and Xuebin Qin, 23 January 2026, Frontiers in Immunology.
DOI: 10.3389/fimmu.2026.1755141

This research was supported by the American Heart Association Long COVID Impact Project (AHA962950), the National Institutes of Health, including P51OD011104-62 and R01HL165265, and institutional funding.

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